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Nat Immunol. 2019 Apr;20(4):447-457. doi: 10.1038/s41590-019-0334-0. Epub 2019 Mar 4.

SLAM receptors foster iNKT cell development by reducing TCR signal strength after positive selection.

Author information

1
Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
2
Bioinformatics Core Facility, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
3
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
4
Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
5
Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada. andre.veillette@ircm.qc.ca.
6
Department of Medicine, University of Montréal, Montréal, Québec, Canada. andre.veillette@ircm.qc.ca.
7
Department of Medicine, McGill University, Montréal, Québec, Canada. andre.veillette@ircm.qc.ca.

Abstract

Invariant natural killer T cells (iNKT cells) develop through an incompletely understood process that requires positive selection by CD4+CD8+ double-positive thymocytes and SLAM family receptors (SFRs). Here we found that SFRs promoted the development of iNKT cells by reducing the strength of the T cell antigen receptor (TCR) signal after positive selection. This effect improved the survival of iNKT cells and their responses to antigen. Loss of SFRs upregulated the expression of inhibitory receptors, including PD-1, on iNKT cells to mitigate the deleterious effect of SFR deficiency. The role of SFRs could be mimicked by expression of SLAMF6 alone in SFR-deficient mice, and this involved the adaptor SAP-kinase Fyn complex and the phosphatase SHP-1. Thus, SFRs foster iNKT cell development by attenuating TCR signal strength after positive selection.

PMID:
30833791
DOI:
10.1038/s41590-019-0334-0

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